REGULATION OF THE EXPRESSION OF NMDA RECEPTOR SUBUNITS IN RAT CEREBELLAR GRANULE CELLS - EFFECT OF CHRONIC K-INDUCED DEPOLARIZATION AND NMDA EXPOSURE()

The influence of K+-induced membrane depolarization and NMDA treatment on the regulation of NMDA receptor subunit (NR) expression was invest igated during the development of granule cells in culture, as a follow up of previous work on NMDA receptor activity. In spite of the increas e in NMDA receptor activity elicited by these treatments (K25 or K10 NMDA cultures), the main developmental changes in receptor mRNA level s were similar to those in untreated cells (K10) (a threefold increase in total NMDA receptor mRNA, quantitative dominance of NR1 mRNA, late expression of NR2C, and virtual absence of NR2D). However, high K+ an d NMDA treatment resulted in a greater increase of NR2A mRNA levels an d a retardation in the developmental changes in the relative amounts o f NR2B and NR2C mRNAs. The correspondence between NMDA receptor activi ty and the amount of NR1 and NR2A subunit proteins was excellent, the rank order being K25 > K10 + NMDA > K10 at 9 days in vitro. Because th e increase in subunit mRNA was not always paralleled by an increase in subunit protein, the control of NMDA receptor expression involves cri tically, in addition to gene transcription, regulation of translationa l and/or posttranslational events.